Regulation of eosinophil and neutrophil apoptosis - similarities and differences

Apoptosis is the most common form of physiologic cell death and a necessary process to maintain cell numbers in multicellular organisms. In many chron ic inflammatory diseases, reduced cell death of different types of granuloc ytes is one important mechanism for cell accumulation. Granulocytes are con stantly produced in large amounts in the bone marrow and the same numbers d ie, under normal circumstances, within a defined time period. Changing the rate of apoptosis rapidly changes cell numbers in such systems. Overexpress ion of IL-5 appears to be crucial for delaying eosinophil apoptosis in many allergic disorders, whereas overexpression of GM-CSF and G-CSF is associat ed with suppression of neutrophil apoptosis in bacterial and non-bacterial inflammations. Cytokine withdrawal leads to the induction of apoptosis both in vitro and in vivo. In contrast to the role of survival cytokines, littl e is known about the role of death factors and their receptors in thr regul ation of granulocyte apoptosis. Recent observations suggest a role for mito chondria in both eosinophil and neutrophil apoptosis, although the mechanis ms that trigger mitochondria to release pro-apoptotic factors remain to be determined. Besides similarities, there are differences in the regulation o f apoptosis between these granulocyte subtypes that include both expression and function of Bcl-2 and caspase family members. The identification of di fferences in the apoptosis regulation may help to define new molecular targ ets that allow specific induction of either eosinophil or neutrophil apopto sis by pharmacological means.